Alpha-1 antitrypsin inhibits formaldehyde-induced apoptosis of human peritoneal mesothelial cells

Lim, Jeong-Hoon; Park, Sang Mi; Yook, Ju-Min; Ahn, Ji-Sun; Choi, Soon-Youn; Oh, Sehyun; Jung, Hee-Yeon; Choi, Ji-Young; Cho, Jang‐Hee; Park, Sun-Hee; Kim, Yong-Lim; Kim, Chan‐Duck

doi:10.1177/0896860819887288

Cited by 4 publications

(6 citation statements)

References 34 publications

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“…We have focused on the effects of AAT on renal fibrosis, inflammation, and apoptosis. AAT plays an important role not only in protease inhibition, but also in inflammation inhibition and tissue protection [ 13 ]. AAT modulates both the activation and maturation of antigen-presenting cells [ 19 , 20 , 21 ], inhibition of various caspases, and improvement of the mitochondrial membrane stability [ 22 ].…”

Section: Discussionmentioning

confidence: 99%

“…AAT has a broad range of inhibitory functions, including anti-inflammatory properties and, as a result, can limit tissue injury resulting from proteases [ 12 ]. Moreover, AAT protects against apoptosis in various types of cells, such as peritoneal mesenchymal cells, beta cells, and hepatocytes [ 13 , 14 , 15 ]. In particular, it is known that the AAT’s inhibitory function of cysteine proteases of the caspase family, such as caspase-3, plays an important role in preventing apoptosis [ 15 ].…”

Section: Introductionmentioning

confidence: 99%

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Renoprotective Effects of Alpha-1 Antitrypsin against Tacrolimus-Induced Renal Injury

Lim

et al. 2020

IJMS

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The protective effects of alpha-1 antitrypsin (AAT) in tacrolimus (TAC)-induced renal injury was evaluated in a rat model. The TAC group rats were subcutaneously injected with 2 mg/kg TAC every day for four weeks. The TAC with AAT group was cotreated with daily subcutaneous injections of TAC and intraperitoneal injections of AAT (80 mg/kg) for four weeks. The effects of AAT on TAC-induced renal injury were evaluated using serum biochemistry, histopathology, and Western blotting. The TAC injection significantly increased renal interstitial fibrosis, inflammation, and apoptosis as compared to the control treatment. The histopathological examination showed that cotreatment of TAC and AAT attenuated interstitial fibrosis (collagen, fibronectin, and α-SMA staining), and α-SMA expression in Western blotting was also decreased. Immunohistochemical staining for inflammation (osteopontin and ED-1 staining) revealed improved interstitial inflammation in the TAC with AAT group compared to that in the TAC group. The TAC treatment increased renal apoptosis compared to the control treatment, based on the results of increased immunohistochemical staining of terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL), increased caspase-3 activity, and lower Bcl-2 to Bad expression ratio. However, AAT cotreatment significantly changed these markers and consequently showed decreased apoptosis. AAT protects against TAC-induced renal injury via antifibrotic, anti-inflammatory, and antiapoptotic effects.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Renoprotective Effects of Alpha-1 Antitrypsin against Tacrolimus-Induced Renal Injury

Lim

et al. 2020

IJMS

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“…GSK3β, a serine/threonine protein kinase, plays a critical role in the regulation of Cyclin D1 expression at both mRNA and protein levels (6). We next evaluated whether AAT overexpression led to enhanced GSK3β expression in iAAT-MSCs compared to iMSCs.…”

Section: Aat-mscs Expressed a Similar Amount Of Gsk3β And β-Catenin C...mentioning

confidence: 99%

“…AAT is a protease inhibitor produced in the liver, protecting the lungs and other organs from neutrophil elastase damage [5]. However, independent of these antiprotease effects, AAT exhibits unique properties such as apoptosis inhibition and promotion of cell proliferation [6,7]. Previous studies have indicated that human AAT-overexpressing mesenchymal stem cells (AAT-MSCs) improve the innate properties of naive MSCs.…”

Section: Introductionmentioning

confidence: 99%

Overexpression of Alpha-1 Antitrypsin Increases the Proliferation of Mesenchymal Stem Cells by Upregulation of Cyclin D1

Wolf,

Muralidharan,

Lee

et al. 2024

IJMS

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Alpha-1 antitrypsin-overexpressing mesenchymal stromal/stem cells (AAT-MSCs) showed improved innate properties with a faster proliferation rate when studied for their protective effects in mouse models of diseases. Here, we investigated the potential mechanism(s) by which AAT gene insertion increases MSC proliferation. Human bone marrow-derived primary or immortalized MSCs (iMSCs) or AAT-MSCs (iAAT-MSCs) were used in the study. Cell proliferation was measured by cell counting and cell cycle analysis. Possible pathways involved in the pro-proliferation effect of AAT were investigated by measuring mRNA and protein expression of key cell cycle genes. Interval cell counting showed increased proliferation in AAT-MSCs or iAAT-MSCs compared to their corresponding MSC controls. Cell cycle analysis revealed more cells progressing into the S and G2/M phases in iAAT-MSCs, with a notable increase in the cell cycle protein, Cyclin D1. Moreover, treatment with Cyclin D1 inhibitors showed that the increase in proliferation is due to Cyclin D1 and that the AAT protein is upstream and a positive regulator of Cyclin D1. Furthermore, AAT’s effect on Cyclin D1 is independent of the Wnt signaling pathway as there were no differences in the expression of regulatory proteins, including GSK3β and β-Catenin in iMSC and iAAT-MSCs. In summary, our results indicate that AAT gene insertion in an immortalized MSC cell line increases cell proliferation and growth by increasing Cyclin D1 expression and consequently causing cells to progress through the cell cycle at a significantly faster rate.

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“…Peritonitis is a common clinical symptom of GPS infection [4,9,10] and may stem from the impairment of inflammation-induced apoptosis [11]. Meanwhile, numerous studies have shown that the effective treatment of peritonitis is closely related to the regulation of apoptosis [12][13][14]. As reported, apoptosis inhibitor of macrophage ameliorates fungal induced peritonitis injury in mice [14], and short-term regulation of apoptosis may help Molecules 2022, 27, 5083 2 of 10 accelerate recovery after peritonitis and prevent irreversible peritoneal damage [15].…”

Section: Introductionmentioning

confidence: 99%

Baicalin Alleviate Apoptosis via PKC-MAPK Pathway in Porcine Peritoneal Mesothelial Cells Induced by Glaesserella parasuis

Zhou

Wang

et al. 2022

Molecules

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Glaesserella parasuis (GPS), a causative agent of Glässer’s disease, is thought to be the main fatal cause of peritonitis in swine, thus resulting in high mortality and morbidity and significant economic losses to the swine industry. However, the mechanisms of GPS infection-induced apoptosis and possible therapeutic pathway for GPS infection in peritonitis remain unclear. Baicalin has important biological functions during disease treatment, such as antiviral, bacterial inhibition, anti-apoptosis, and anti-inflammatory. However, whether baicalin has anti-apoptotic effects during the process of GPS infection in peritonitis is unclear. In the present study, the anti-apoptotic effect and mechanisms of baicalin in GPS infection-induced apoptosis were investigated in porcine peritoneal mesothelial cells (PPMC). The results showed that baicalin could inhibit the apoptosis rate occurrence of PPMC induced by GPS to various degrees and inhibit the expression of apoptosis-related genes and cleaved caspase-3. Meanwhile, baicalin significantly antagonized the expression of p-JNK, p-p38, and p-ERK induced by GPS in PPMC. These findings for the first time demonstrate that baicalin exerted the effect of antagonizing GPS induced apoptosis in PPMC by inhibiting the activation of the PKC-MAPK pathway and could be a therapeutic option in the management of GPS infection.

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Alpha-1 antitrypsin inhibits formaldehyde-induced apoptosis of human peritoneal mesothelial cells

Cited by 4 publications

References 34 publications

Renoprotective Effects of Alpha-1 Antitrypsin against Tacrolimus-Induced Renal Injury

Renoprotective Effects of Alpha-1 Antitrypsin against Tacrolimus-Induced Renal Injury

Overexpression of Alpha-1 Antitrypsin Increases the Proliferation of Mesenchymal Stem Cells by Upregulation of Cyclin D1

Baicalin Alleviate Apoptosis via PKC-MAPK Pathway in Porcine Peritoneal Mesothelial Cells Induced by Glaesserella parasuis

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